Marzia Indrigo, Ilaria Morella, Daniel Orellana, Raffaele d'Isa, Alessandro Papale, Riccardo Parra, Antonia Gurgone, Daniela Lecca, Anna Cavaccini, Cezar M Tigaret, Alfredo Cagnotto, Kimberley Jones, Simon Brooks, Gian Michele Ratto, Nicholas D Allen, Mariah J Lelos, Silvia Middei, Maurizio Giustetto, Anna R Carta, Raffaella Tonini, Mario Salmona, Jeremy Hall, Kerrie Thomas, Riccardo Brambilla, Stefania Fasano
Cell signaling is central to neuronal activity and its dysregulation may lead to neurodegeneration and cognitive decline. Here, we show that selective genetic potentiation of neuronal ERK signaling prevents cell death in vitro and in vivo in the mouse brain, while attenuation of ERK signaling does the opposite. This neuroprotective effect mediated by an enhanced nuclear ERK activity can also be induced by the novel cell penetrating peptide RB5. In vitro administration of RB5 disrupts the preferential interaction of ERK1 MAP kinase with importinα1/KPNA2 over ERK2, facilitates ERK1/2 nuclear translocation, and enhances global ERK activity...
October 4, 2023: EMBO Molecular Medicine